A large number of drugs and therapeutic agents have been developed to treat diseases, but problems regarding the passage of drugs through biological barriers (for example, skin, oral mucosae and blood-brain barriers) and the efficiency of drug delivery remain to be solved for in vivo delivery of the drugs.
In general, drugs are orally administered as a tablet formulation or a capsule formulation, but a large number of drugs are not effectively delivered only by such administration method because the drugs are digested in or absorbed into the gastrointestinal tract or are destroyed by mechanisms in the liver, etc. In addition, some drugs cannot be effectively diffused through mucous membranes in the intestines. Also, the patient's compliance also has become a challenge (for example, in the case of critical patients who need to take medicine at certain intervals or cannot take medicine, etc.).
Another common technology for delivering drugs is to use a conventional injection needle. This technology is more effective than oral administration, but may cause pain in an injected area, local damage to skin, bleeding, and infections in the injected area.
To solve the above problems, various microstructures including microneedles have been developed. The microneedles currently developed have been generally used to deliver drugs to human bodies, collect blood, and detect analytes from the human bodies. The microneedles are characterized by piercing the skin in a minimally invasive manner. For painless piercing of the skin, it is important to determine the diameter of a top of the microneedle for the needle's minimum sharpness. Also, since the microneedle needs to pierce the 10 to 20-μm-thick stratum corneum, which is the most potent barrier of the skin, the microneedle needs to have a sufficient physical hardness. Further, a suitable length of the microneedle to deliver drugs to capillary vessels should be considered to enhance the efficiency of drug delivery.
Meanwhile, a microstructure is often fabricated in the form of a patch including a number of microneedles so as to inject the microneedles into the skin. However, the microneedles have a drawback in that, when they are applied to the skin in the form of a patch, a patient must wait until the microneedles are fully dissolved (for approximately 2 hours) before removing the patch. Also, the microneedles in the form of a patch have a limit in application to a hairy region. Further, some people frequently have an allergic reaction to glutinous substances present in the patch.
Dissolving microneedles (DMNs) of the present invention are microneedles obtained by polymer polymerization, and a drug is encapsulated in a matrix of each of the DMNs. Insertion of the DMNs into the skin catalyzes the decomposition of a polymeric compound, and thus the drug is systemically or locally delivered. Unlike a subcutaneous injection, the DMNs are biocompatible and do not produce biologically hazardous materials (3, 20). Also, the DMNs are more dose-efficient than immunization by subcutaneous injection (21-23). In recent years, various patches are being widely used to apply the DMNs, but the drug delivery efficiency is low due to a number of parameters regarding skin elasticity, etc., and the DMNs are not completely inserted into the skin (17, 24, and 25). Further, the compound used in the patch has problems in that it may cause various inflammations or allergic reactions in the skin, and lasting adhesion is difficult when it is applied to a joint area or hairy skin, and patients should wait for a long period of time until the drug is completely dissolved (26).
To solve the problems of the prior art regarding the recent DMN-mediated drug delivery, various methods have been designed (20, 24, 27, and 28). However, these methods have focused on improving the common delivery efficiency of DMNs, but there is no mention of a basic solution to problems regarding the incomplete insertion of the DMN patch.
Therefore, there has been a constant demand for novel microstructures capable of solving the above problems of the prior art.
Throughout this specification, a number of research papers and patent documents are cited and provided in parentheses. The disclosures of the cited research papers and patent documents are incorporated herein by reference in their entirety to more fully describe the state of the art to which the present invention pertains and the contents of the present invention.